In the midst of a flu epidemic (in the USA), some good news?researchers think they've solved the age-old medical mystery of why shy, sensitive people are more vulnerable to infectious disease.

Is personality related to disease?

From the common cold to life-threatening infections, researchers have known for a while that shy people?whom ancient Greek physicians described as having a 'melancholic temperament'?are more vulnerable to infectious diseases than their more outgoing counterparts.

'We knew that these shy, sensitive introverted people were more vulnerable to infectious diseases,' says Steve Cole, assistant professor of hematology-oncology at the David Geffen School of Medicine and a member of the UCLA AIDS Institute.

'But we didn't know why that was. What physical biology leaves them more vulnerable to these kinds of diseases?'

To find an answer Cole studied people with AIDS, because in one of his previous studies 'shy sensitive individuals showed increased vulnerability to HIV disease progression. They got sick and died something on the order of three years sooner than the remainder of the samples that we were looking at. And this was in the context of about a 10-year disease progression span. So this was about a 30 percent acceleration in disease progression.'

Cole recruited 54 men with HIV, all healthy and still in the early stages of the disease, and tested them for their level of shyness with a standard questionnaire.

Then he took physical measurements of autonomic nervous system activity?such as blood pressure and heart rate?in response to various stressful stimuli (exercises that required a quick response, an irritating beeping noise, and demanding mental arithmetic).

'We essentially averaged all of these scores together to give each individual a measure of how reactive their autonomic nervous system was in general,' says Cole. The autonomic nervous system controls many organs and muscles in the body, and is especially important in stressful situations that require the 'fight or flight' mechanism.

The men who rated high on the shyness scale also showed elevated responses to stress. 'They had higher resting heart rate, less variability in their heart rate? higher blood pressure, and higher what's called skin conductance level, or the amount of moisture in their skin, which is also a measure of autonomic nervous system activity,' says Cole.

Over the following months Cole monitored each participant's HIV viral load and his level of T-cells, the body's immune cells which HIV infect. 'We found that these shy sensitive individuals with high autonomic nervous system activity also had something on the order of tenfold higher levels of HIV virus in their blood,' says Cole.

'This is the primary indicator of how fast the virus is replicating in their body, and also the primary prognostic factor for how soon they're going to get sick.'

Cole reported in a previous study that norepinephrine, a chemical that our bodies release under stress, causes certain proteins to poke out of our T-cells?the proteins that the AIDS virus attaches to.

'They're like cellular Velcro,' says Cole. 'The chemicals released by the body during stress responses make the cell a stickier target for the HIV virus.'

This, he thinks, is the mechanism that causes shy people to become sick more often and faster than others. So it's not just shyness, but the stress that shy people are constantly experiencing that makes them more vulnerable to disease.

'So it's probably true that anybody who has high levels of autonomic nervous system activity is more vulnerable to infectious diseases,' says Cole.

'It looks as though this phenomena is general throughout nature?that stress reduces our resistance to infectious disease. And what our data is suggesting increasingly is it does that in part by making our bodies a more fertile place for the virus to grow.'

Next Cole will test whether drugs that block norepinephrine can help reduce the amount of HIV in shy patients. He's also looking into what other diseases besides AIDS are aided by the same mechanism.

This research was published in the December 15, 2003 issue of the journal Biological Psychiatry, and was funded by the US Public Health Service; the National Institute of Mental Health (NIMH); UCLA AIDS Institute; Pendelton Foundation; Norman Cousins Center at UCLA; Veterans Administration Medical Research Foundation; and Roche Diagnostics, and the University of California Universitywide AIDS Research Program. His research on norepinephrine was published in the October 23, 2001 issue of the Proceedings of the National Academy of Sciences.